Predicting Responses to PTSD Treatment With Iris and Cardiovascular Tests

NCT03539614 | Active Not Recruiting Phase 3 DMC FDA Drug

• 2 other identifiers: MHBB-003-17F1IK2CX001774-01
• Study Type: interventional
• Target: 87
• Locations: 1 country
• Sites: 1

Brief Summary

Posttraumatic stress disorder (PTSD) affects many individuals who experience a traumatic event. There are a variety of treatment options for PTSD, including psychotherapy (talk therapy) options, as well as medications, such as the drug prazosin. Each of the treatment options available is effective at significantly reducing the symptoms of PTSD in some, but not all, individuals with PTSD. However, investigators are not yet able to predict in advance who is likely to respond to which of the available treatments. Neither are the investigators able to explain what changes in the brain after exposure to a traumatic stressors, and why it results in persistent symptoms of PTSD for some people, but not for others. In this study, the investigators are testing two things: First, is testing whether two simple, easy tests of how an individual's blood pressure changes with standing and how an individual's eye reacts to a pulse of light may be able to predict whether that person is likely to respond to the medication prazosin for PTSD. Second, is testing whether those who have been exposed to a traumatic stress show differences in how their body regulates the response to the stress-signal noradrenaline.

Conditions

Posttraumatic Stress Disorder

Keywords

Prazosin; Nightmares; N-of-1

Outcome Measures

Primary Outcomes (1)

• Change in total PTSD Checklist for DSM 5 (PCL5) score

  The PTSD Checklist for DSM 5 is a self-reported rating scale where an individual rates the severity of each symptom of PTSD on a likert scale. The ratings on individual items are summed to create a total score, which ranges from 0 to 80, with higher scores indicating more symptoms. The relationship between changes in participants' total PCL scores at different time points and prazosin exposure - and whether this relationship is moderated by baseline biomarker values - will be analyzed using a linear mixed effects model.

  The PCL5 total score is assessed at baseline, during each stage of the study, and at the endpoint of the study. Thus, measurements will be scheduled to occur at the following time points, relative to the baseline visit: 0, 4, 8, 9-12, 16, and 20 weeks

Study Arms (2)

Open label, blinded discontinuation, prazosin, placebo

EXPERIMENTAL

All participants in this study will begin with 8 weeks of active treatment (prazosin), followed by a 4 week "blinded discontinuation" block where they will take a capsule that will start out as active treatment (prazosin), but will at some point change to placebo. Following these phases of the study, participants will be randomized to two arms. In this first arm, participants will spend 4 weeks on active treatment (prazosin), followed by 4 weeks on placebo.

Drug: Prazosin; Drug: Placebo

Open label, blinded discontinuation, placebo, prazosin

EXPERIMENTAL

All participants in this study will begin with 8 weeks of active treatment (prazosin), followed by a 4 week "blinded discontinuation" block where they will take a capsule that will start out as active treatment (prazosin), but will at some point change to placebo. Following these phases of the study, participants will be randomized to two arms. In this second arm, participants will spend 4 weeks on placebo, followed by 4 weeks on active treatment (prazosin).

Drug: Prazosin; Drug: Placebo

Interventions

Prazosin DRUG

This is an antagonist of the alpha1 receptor for noradrenaline. It is FDA approved for the treatment of hypertension, and has also been used for benign prostatic hypertrophy (BPH). Most recently, it has been found to be helpful for symptoms of PTSD in some but not all participants.

Also known as: Minipress

Open label, blinded discontinuation, placebo, prazosin; Open label, blinded discontinuation, prazosin, placebo

Placebo DRUG

This is a capsule containing an inert substance, in order to provide blinding to participants and study staff of when participants are on active medication and when they are not during the later portions of the trial.

Open label, blinded discontinuation, placebo, prazosin; Open label, blinded discontinuation, prazosin, placebo

Eligibility Criteria

• Age: 21 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Veteran of the U.S. Armed Forces
• Woman of childbearing potential must agree to abstain from sexual relations that could result in pregnancy or use an effective method of birth control acceptable to both participant and study clinician during the study. Men are not required to use contraception during the study.

You may not qualify if:

• Psychiatric:
• Any known diagnosis of a primary psychotic or major neurocognitive disorder, including schizophrenia, brief psychotic disorder, or Alzheimer's or other dementia, as well as bipolar type I
• Severe psychiatric instability or severe situational life crises, including evidence of being actively suicidal or homicidal, or any behavior which poses an immediate danger to participant or others.
• Medical:
• Significant bilateral visual loss (would preclude performing the PLR measurements)
• Current pregnancy or lactation
• Allergy or previous adverse reaction to prazosin or other alpha-1 antagonist
• Acute or unstable chronic medical illness, including unstable angina, recent myocardial infarction (within 6 months), congestive heart failure, preexisting hypotension (systolic \<110) or orthostatic hypotension (systolic drop \> 20mmHg after two minutes standing or any drop accompanied by dizziness); autoimmune disorders; insulin-dependent diabetes
• Chronic renal or hepatic failure, acute pancreatitis, Meniere's disease, benign positional vertigo, or narcolepsy
• Medication / treatment:
• Any use within the 7 days prior to baseline of prazosin, doxazosin, clonidine, guanfacine, trazodone, or nonbenzodiazepine hypnotics, and/or unwillingness to avoid these medications for the duration of the study
• Use of avanafil (Stendra), sildenafil (Viagra), tadalafil (Cialis), and vardenafil (Levitra) will be not be permitted during the study dose titration period because of increased risk of hypotension in combination with alpha-1 blockers, but will be allowed at 1/2 the usual starting dose following dose titration
• Current use of nitrates, or of alternative medications or supplements with significant vasodilatory properties (e.g., nitrate containing supplements) Participants may also be excluded at the discretion of PI or study clinicians if they appear to be unsuitable for this research study for a reason not detailed here.

Sponsors & Collaborators

• VA Office of Research and Development: lead

Study Sites (1)

VA Puget Sound Health Care System Seattle Division, Seattle, WA

Seattle, Washington, 98108-1532, United States

Location

MeSH Terms

Conditions

Stress Disorders, Post-Traumatic

Interventions

Prazosin

Condition Hierarchy (Ancestors)

Stress Disorders, Traumatic; Trauma and Stressor Related Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Quinazolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Rebecca C. Hendrickson, MD PhD

  VA Puget Sound Health Care System Seattle Division, Seattle, WA

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, OUTCOMES ASSESSOR
• Masking Details: During the portion of the study where participants are receiving either placebo or blinded prazosin, the participants, care providers, and outcomes assessors will all be blinded as to whether the participant is at that time receiving prazosin or placebo.
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: FED
• Responsible Party: SPONSOR

Model Details: This study is a modified cross-over study, also called an aggregated N-of-1 study. Each participant who meets criteria for participation in and completes the treatment portion of the study will spend time on open-label prazosin, blinded prazosin, and placebo.

Study Record Dates

• First Submitted: May 2, 2018
• First Posted: May 29, 2018
• Study Start: June 4, 2018
• Primary Completion: January 1, 2026
• Study Completion (Estimated): June 1, 2026
• Last Updated: February 17, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)